Breaker discovers new ‘world’

Yale researchers have found an ancient relic used by our ancestors, but it is a lot older than Sumerian pottery. A team of biologists including Yale professor Ronald Breaker discovered molecular evidence of a primordial “RNA world” that existed four billion years ago, before DNA and proteins evolved.

The researchers have identified a highly efficient form of “riboswitch” — a part of RNA that regulates gene expression — that responds to a molecule involved in cellular energy production. This genetic switch shows that RNA is capable of a variety of functions, supporting the evolutionary theory of an era when nearly all life processes were controlled by RNA.

“This research suggests that RNA is a lot more interesting and capable than we realized,” Zasha Weinberg, a graduate student at Washington University who developed software contributing to the discovery, said. “I think that this will make people change the focus of their research more to RNA.”

Messenger RNA is a genetic molecule that carries information from DNA to the site where proteins are synthesized according to the DNA’s specifications. The researchers were studying “riboswitches,” regulatory parts of mRNA that react to conditions inside the cell and determine which genes are expressed. A newly discovered riboswitch that helps regulate energy production is the first found to utilize cooperative binding, a process that makes it highly sensitive to the cell’s metabolic needs.

Though proteins regulate most gene expression in modern organisms, this highly efficient riboswitch suggests RNA is also capable of such regulation. This all-purpose molecule supports the theory of the “RNA World,” an era of life before protein existed.

“These molecules help validate the ‘RNA World’ hypothesis and therefore help validate a more scientific basis for the origin of life,” Breaker said.

The new riboswitch regulates glycine, an unusually small molecule that is a component in energy production. The biological importance of glycine as well as the complexity required to regulate a molecule of its size casts RNA in a new light.

The new riboswitch was created in an experiment that simulated molecular evolution in early life.

“Evolution that has occurred over billions of years on Earth is repeated in a test tube,” said Maumita Mandal, another researcher on the project who is currently working at University of California, Berkeley.

Riboswitches are known to exist in modern bacteria, but they have not yet been found in higher organisms.

“The organisms of the ancient RNA world might not be entirely extinct,” Breaker said. “Bits and pieces of their molecules could still lay hidden in all our cells.”

If certain riboswitches are found only to exist in bacteria, medications could be invented to target the riboswitches, creating a new weapon against infection. The Defense Advanced Research Projects Agency has already offered to support this line of research, especially for its possible impact on biological warfare, but the researchers said they were excited for possible medicinal uses.

“It’s actually kind of a win-win situation,” said Weinberg. “If riboswitches were found only in bacteria, we could make more promising antibiotics. If we found them in people, they would be more directly relevant to human health. Either way, there’s some potential medical applications.”